Figure 7. Downstream signaling molecules activated by PFN2 are Smad2/3 in H446 cells and pERK in HUVEC cells. Smad2 and Smad3 expression is increased in H446-OE (A) but decreased in H446-KD (B). Smad3 inhibitor could impede the function of PFN2 in promoting the proliferation (P=0.9279, 0.0030, 0.0004, and 0.000 at 6 h, 12 h, 18 h, and 24 h, respectively) (C), migration (P=0.0123) (D), and invasion (P=0.0136) (E) of H446 cells. pERK and tERK expression in HUVEC cells co-cultured with H446-OE-exo is upregulated (F), whereas the expression in those co-cultured with H446-KD-exo is downregulated (G). ERK inhibitor could impede the function of PFN2 in promoting the migration (P=0.0333) (H) and tube formation ability (P=0.0238) of ECs (I).